Dual roles of TRIM3 in colorectal cancer by retaining p53 in the cytoplasm to decrease its nuclear expression

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Colorectal cancer (CRC) is a heterogeneous disease influenced by genetic and environmental factors.
• TP53 mutations are common in CRC and critical for tumor progression.
• Chemotherapy resistance is a major challenge in advanced CRC treatment.

Purpose of the Study:

• To investigate the role of TRIM3, a newly identified tumor-associated gene, in colorectal cancer.
• To elucidate the interaction between TRIM3 and p53 (wild-type and mutant) in CRC pathogenesis.
• To evaluate TRIM3's potential in overcoming chemotherapy resistance in CRC.

Main Methods:

• High-content screening to identify tumor-associated genes in CRC.
• Cell experiments to assess TRIM3's function based on p53 status.
• Co-immunoprecipitation to confirm TRIM3-p53 interaction.
• Analysis of TRIM3's effect on p53 localization and chemotherapy resistance.

Main Results:

• TRIM3 was identified as a tumor-associated gene in CRC.
• TRIM3 exhibits dual roles (tumor-suppressive/tumorigenic) dependent on p53 status.
• TRIM3 directly interacts with the C terminus of p53.
• TRIM3 influences p53 localization, affecting nuclear expression.
• TRIM3 reverses oxaliplatin resistance in mutant p53 CRC cells by degrading nuclear mutant p53 and downregulating multidrug resistance genes.

Conclusions:

• TRIM3 plays a complex role in colorectal cancer, modulated by p53.
• TRIM3's ability to overcome chemotherapy resistance presents a potential therapeutic strategy for mutant p53 CRC.
• Targeting TRIM3 could improve treatment outcomes for CRC patients with p53 mutations.